In Alzheimer’s disease (AD) a progressive neurodegeneration and cognitive decline occurs during the course of the disease and amylloid beta-peptide (Abeta) is believed to play a central role for the molecular pathogenesis of AD. The gamma-Secretase is a key enzyme involved in the processing of the beta-amyloid precursor protein into Abeta. Abeta accumulates in brain and forms plaques in AD brains. One of the mechanism behind neurodegenration in AD is apoptosis due to preservation of gamma secretase activity. Several proteins (presenilin1, presenilin 2, nicastrin, Aph-1 and Pen-2) interact with gamma secretase complex during apoptosis in neuronal cells to make active gamma secretase complexes in apoptotic cells. The fragments corresponding to the PS1 N-terminal fragment and the caspase-cleaved PS1 C-terminal fragment (PS1-caspCTF) were found to form active gamma-secretase complexes when co-expressed in presenilin (PS) knockout cells (1). Mutations in presenilin 1 (PS1) lead to dominant inheritance of early-onset familial Alzheimer’s disease (FAD). These mutations are known to alter the gamma-secretase cleavage of the amyloid precursor protein (APP), resulting in increased ratio of Abeta42/Abeta40 and accelerated amyloid plaque pathology and altered intracellular Ca(2+) homeostasis involving endoplasmic reticulum Ca(2+) stores (2, 3). It is suggested that Presenilin binds to phospholipase D1 through its loop region thereby recruiting golgi/transgolgi network that perturbs gamma secretase activity and Abeta formation.
Numerous mutations in the presenilins are known to cause early-onset familial Alzheimer’s disease (FAD). These mutations are known to alter the gamma-secretase cleavage of the amyloid precursor protein (APP), resulting in increased ratio of Abeta42/Abeta40 and accelerated amyloid plaque pathology in transgenic mouse models. Presenelin 1is a 467 amino acid membrane bound protein with 8 putative TMD. It is believed to be the catalytic domain of gamma secretase complex that catalyzes the intramembrane cleavage of integral membraneproteins such as Notch receptors and beta amyloid precursor protein. Other functions include intracellular signaling and gene expression or in linking chromatin to the nuclear membrane. Some regulatory proteins associated with Resenelin are Nicastrin, NTF, CTF, APH1/2and PEN2. It also interacts with other proteins such as Notch1, cadherin 1, plakophilin 4, dock 3, catenin, HERPUD1, FLNA and FLNB.
The PSEN1-selective antibodies were generated against unique antigenic sequences form near N- and C-terminal peptides for the presenilin gene. The antibodies to PSEN 1 are affinity purified over immobilized antigen based chromatography, and the purified immunoglobulins are stabilized in antibody stabilization buffer. FabGennix Int. Inc., will also provide limited quantities of antigenic blocking peptides for both PSEN-101AP and PSEN-112AP. Antibodies to the Presenelin 2 (PSEN-201AP) protein is also available from FabGennix International Inc. FabGennix Inc. will also conjugate antibodies with secondary enzymes (alk-Pase or HRP) or fluorescent probes upon request at a nominal cost.
For research use only, not for diagnostic or therapeutic use.
Data Sheets
Presenilin1
MSDS
Citations
Search FabGennix Product Citation Data Base
Search
